Changes in contractile response and effect of a calcium antagonist, nimodipine, in isolated intracranial arteries of baboon following experimental subarachnoid hemorrhage

Isolated pial arteries from a previously well-characterized model of experimental subarachnoid hemorrhage (SAH) in baboon were tested for their contractile response to 5-hydroxytryptamine (5-HT), norepinephrine (NE), and prostaglandin F2 alpha (PGF2 alpha) and the effect of the calcium antagonist, nimodipine. Autologous blood was injected cisternally at three times with one-day intervals to a total amount of 11.5-29.5 ml (mean: 18.5 ml), and the animals were killed 7 days after the first injection. Untreated animals served as controls. The degree of maximum contraction (EAm) with 5-HT and NE in the control situation was for the three arteries tested in the order middle cerebral greater than anterior cerebral greater than basilar artery. Experimental SAH markedly increased EAm, by 190-370 percent above control values (depending on type of vessel) for 5-HT and 170-185 percent for NE. In addition, the sensitivity to 5-HT was significantly increased, as evidenced by a left-shift of the concentration-response curve. Previous exposure of the artery to 10(-6) M nimodipine reduced the contractile response of both amines to approximately half, the inhibition being slightly less pronounced post-SAH. When vessels were contracted beforehand with the amines or with PGF2 alpha, followed by administration of increasing amount of nimodipine (10(-9) M to 10(-6) M), a concentration-dependent relaxation was obtained by up to 60 percent of the original level. This relaxing effect was significantly less following SAH in the experiments with NE and PGF2 alpha compared to 5-HT; the contraction in the presence of 5-HT did not differ before and after experimental SAH. The experiments show that SAH markedly enhances the intrinsic activity for both 5-HT and NE. Nimodipine inhibits the contractile response less efficiently following experimental SAH. The difference in the responsiveness to 5-HT on the one hand, and to NE and PGF2 alpha on the other, could be due to differences in the blood-induced alterations of those calcium channels that are influenced by the calcium antagonist, nimodipine